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Biomedical subjects

Hajnalka Vágó

Publications and source records attributed to Hajnalka Vágó.

11 recordsLinked to original sources

Mesenteric vascular dysfunction after cardiopulmonary bypass with cardiac arrest is aggravated by coexistent heart failure.

Although patients suffering from heart failure (HF) have an increased incidence of nonocclusive mesenteric ischemia after opened heart surgery, the impact of cardiopulmonary bypass with cardiac arrest (CPB) on mesenteric vascular circulation in such situation remains unexplored. Therefore, the present study investigates the effects of CPB on mesenteric vascular reactivity, regional metabolism, and oxidative stress in an experimental model of HF. Volume-overload HF was induced in six dogs by bilateral femoral arteriovenous fistula. Six sham-operated dogs were used as controls. Eight weeks later, the short-term effects of 90 min of CPB were assessed in vivo during acute experiments. The significant increase in left ventricular end-diastolic volume in HF animals did not influence the vasodilator response of the superior mesenteric artery to acetylcholine (ACH) and nitroprusside (SNP) under baseline conditions. However, reduced mesenteric oxygen delivery, increased oxygen extraction, and lactate release were found during CPB in the HF group. In addition, an increased free radical production was assessed in the HF group during (89 +/- 23 x 10 relative light units [RLU]) and after CPB (93 +/- 15 x 10 RLU) compared with controls (45 +/- 15 and 49 +/- 7 x 10 RLU, respectively). Finally, 90 min of CPB led to a more pronounced decrease of ACH- (-22% +/- 5% vs. -42% +/- 9%, P < 0.05) and SNP- (-14% +/- 4% vs. -50% +/- 7%, P < 0.002) induced mesenteric vasodilations in the HF group compared with controls. We conclude that coexistent HF significantly enhances the pathological effects of CPB on the mesenteric vascular circulation by additionally altering endothelial and smooth muscle vascular function consequent to augmented oxidative stress.

Acetylcholine↗

Parasympathetic cardiac nerve stimulation with implanted coronary sinus lead.

A patient with drug-refractory paroxysmal atrial fibrillation associated with rapid ventricular rate underwent biatrial pacemaker implantation. During elective replacement of the pacemaker, a significant voltage- and frequency-dependent decrease in ventricular rate was achieved by high-frequency electrical stimulation (17 Hz) of parasympathetic cardiac nerves innervating the AV node with the implanted bipolar coronary sinus electrode. The negative dromotropic effect of parasympathetic stimulation was eliminated by intravenous administration of 1-mg atropine.

Anti-Arrhythmia Agents↗

Endothelin gene expression during ischemia and reperfusion.

Endothelin-1 (ET-1) probably plays an important role in myocardial damage in acute ischemia. Coronary sinus ET-1 and its precursor big endothelin-1 (big ET-1) levels and also tissue levels of preproendothelin-1 mRNA (ET-1 mRNA) were investigated in an in vivo canine ischemia-reperfusion model in nine consecutive mongrel dogs, surviving 30-minute ligation of the left descending coronary artery followed by a 90-minute reperfusion period. Samples were collected before and at the end of ischemia and during reperfusion. ET-1 and big ET-1 were obtained by immunoprecipitation and detected by western blotting. The ET-1 mRNA level was assessed by reverse transcription-polymerase chain reaction. During ischemia the plasma ET-1 levels and big ET-1 levels did not change significantly, while the myocardial ET-1 mRNA level decreased to 57.8%. During reperfusion an increase of the coronary sinus ET-1 and big ET-1 levels was observed (control versus reperfusion, 90 minutes; ET-1, 15.2 +/- 4.18 fmol/mL versus 23.2 +/- 5.23 fmol/mL, P < 0.01; big ET-1, 14.7 +/- 5.9 fmol/mL versus 27.2 +/- 7.1 fmol/mL, P < 0.001). Simultaneously, the ET-1 mRNA level increased by 322% relative to the ischemic and by 214% relative to the baseline level. The decrease of ET-1 mRNA during ischemia may be due to degradation and decreased metabolism in the hypoxic cells locally. The elevation of the ET-1 mRNA level during reperfusion indicates rapid big ET-1 synthesis. This was confirmed by the increases in big ET-1 and ET-1 plasma levels. This latter can be associated with the generation of reperfusion arrhythmias or other complications of acute myocardial infarction.

Animals↗

Effect of incessant ventricular tachyarrhythmias on serum endothelin and big-endothelin levels.

Endothelin-1 (ET-1) is a potent endogenous arrhythmogenic substance. The aim of our study was to investigate the changes of serum ET-1 and big-endothelin levels in patients suffering from spontaneous, incessant ventricular tachyarrhythmias. The 11 consecutive patients' (mean age, 59 +/- 11 years) underlying diseases were ischemic heart disease, valvular heart disease, dilated cardiomyopathy, primary electrical disease, and arrhythmogenic right ventricular dysplasia in five cases, three cases, one case, one case, and one case, respectively. The mean ejection fraction was 39 +/- 14%, New York Heart Association functional status was I, II, and III in two cases, four cases, and five cases, respectively. Ventricular tachycardias (VT) were detected in five patients, ventricular fibrillation (VF) in three patients, and VT + VF in three patients. VTs terminated spontaneously in two cases. Six patients required multiple external cardioversion/defibrillation shocks, while implantable cardioverter defibrillators terminated all sustained arrhythmias successfully in four cases. Blood samples were collected during arrhythmias and 24 hours (control) following the last VT/VF episode. Serum ET-1 and big-endothelin levels were measured with western blot analysis after immunoprecipitation. Serum ET-1 and big-endothelin levels were significantly higher during the last VT/VF compared with the control period (ET-1, 65.8 +/- 26.8 fmol/mL versus 53.9 +/- 22.3 fmol/mL, P < 0.05; big-endothelin, 115.2 +/- 39.3 fmol/mL versus 89.2 +/- 25.1 fmol/mL, P < 0.05). There was a negative correlation between the age and big-endothelin level measured at both times (during VT/VF, r = 0.94, P < 0.05; control, r = 0.91, P < 0.05). In conclusion, serum big-endothelin and ET-1 levels were significantly higher during incessant VT/VF, which can be a cause of multiple arrhythmia recurrence.

Adult↗

Magnetic resonance imaging-based biventricular pacemaker upgrade.

This report describes a patient with drug refractory severe chronic ischemic heart failure, atrial fibrillation with bradycardia, and left bundle branch block who had a failed implantation of a biventricular pacemaker because of a high left ventricular pacing threshold. VVI pacemaker implantation had not improved the patient's condition. MRI-guided biventricular pacemaker upgrade had been performed with a left ventricular epicardial lead at the lateral region where a 4-mm thickening during systole had been proven. After 6 months of effective resynchronization, the patient's functional class improved to NYHA II without further need of hospitalization.

Atrial Fibrillation↗

Changes of endothelin-1 and big endothelin-1 levels and action potential duration during myocardial ischemia-reperfusion in dogs with and without ventricular fibrillation.

Myocardial ischemia-reperfusion is associated with increased production of endothelin-1 (ET-1). Moreover, exogenous ET-1 has arrhythmogenic properties. Our aim was to investigate the correlation between endogenous ET-1, big ET-1 levels and epicardial monophasic action potential duration during myocardial ischemia-reperfusion in anesthetized dogs. Thirty-minute myocardial ischemia was followed by a 90-minute reperfusion period in 18 mongrel dogs. The total incidence of ventricular fibrillation (VF) during ischemia and reperfusion was 11.1% and 33.3%, respectively. During ischemia, the monophasic action potential duration at 90% repolarization (MAPD90) decreased significantly (control versus ischemia, 30 minutes, 224.7 +/- 7.1 ms versus 173.8 +/- 7.6 ms; P < 0.05), while during reperfusion a significant prolongation of MAPD90 was observed (ischemia, 30 minutes versus reperfusion, 30 minutes, 173.8 +/- 7.6 ms versus 249.7 +/- 9.9 ms, P < 0.05). During reperfusion ET-1 and big ET-1 levels increased significantly in the coronary sinus and femoral artery (control versus reperfusion, 90 minutes: coronary sinus ET-1, 15.1 +/- 1.4 fmol/mL versus 22.3 +/- 1.1 fmol/mL; big ET-1, 14.7 +/- 1.9 fmol/mL versus 27.4 +/- 2.3 fmol/mL; P < 0.05). The ET-1 concentration increased to a higher level during ischemia in dogs with VF compared with dogs surviving ischemia-reperfusion (non-VF versus VF: control, 15.1 +/- 1.3 versus 15.2 +/- 1.3; ischemia, 30 minutes, 17.6 +/- 1.2 fmol/mL versus 22 +/- 1.6 fmol/mL; P < 0.05), demonstrating a trend of correlation between endothelin levels and development of VF (P = 0.07). ET-1 and big ET-1 levels increased during reperfusion and in the VF group during ischemia; however, there was no correlation between endothelin levels and MAPD90.

Action Potentials↗

Expressed monophasic action potential alternans before the onset of ventricular arrhythmias induced by intracoronary bolus administration of endothelin-1 in dogs.

We showed previously a direct arrhythmogenic effect of the intracoronary infusion of endothelin-1 (ET-1). We aimed to examine the electrophysiological effects of intracoronary bolus administration of ET-1 using monophasic action potential (MAP) recordings. Eight mongrel dogs received boli of ET-1 (1 and 2 nmol) into the left anterior descending coronary artery. These intracoronary ET-1 boli rapidly caused a marked decrease in coronary blood flow (1 nmol, 78+/-7%; 2 nmol, 89+/-7%). Ischaemic changes of MAP morphology, a decrease in upstroke velocity (baseline, 1.78+/-0.2 V/s; 1 nmol, 0.95+/-0.18 V/s; 2 nmol, 0.45+/-0.21 V/s; P<0.01) and a decrease in MAP duration at 90% repolarization (MAPD(90)) [1 nmol, from 191+/-3 to 176+/-5 ms (P<0.05); 2 nmol, from 212+/-4 to 180+/-8 ms (P<0.05)] occurred after ET-1 bolus administration. However, at 7-10 min after the 1 nmol bolus, a significant increase in MAPD(90) was observed (10 min, in the left ventricular anterior epicardial region: from 191+/-3 to 206+/-6 ms; P<0.05). The incidence of ventricular arrhythmias was as follows: after the 1 nmol ET-1 bolus: ventricular tachycardia, 3/8 animals; ventricular fibrillation, 1/8; after the 2 nmol ET-1 bolus: ventricular tachycardia, 5/7; ventricular fibrillation, 5/7. MAP alternans was present in each animal (1 nmol, 18.2+/-5.8%; 2 nmol, 10.8+/-2.5%). Thus electrophysiological and coronary blood flow changes indicate the predominance of an ischaemic arrhythmogenic effect of the bolus administration of ET-1 (shortening of action potential duration; appearance of MAP alternans), whereas the observed delayed prolongation of MAPD(90) suggests a direct arrhythmogenic effect of ET-1. The expressed MAP alternans could have a pathogenic role in the onset of ventricular arrhythmias induced by an intracoronary bolus of ET-1.

Action Potentials↗

The ET(A) receptor antagonist LU 135252 has no electrophysiological or anti-arrhythmic effects during myocardial ischaemia/reperfusion in dogs.

The anti-arrhythmic effects of ET(A) receptor antagonists during myocardial ischaemia and reperfusion remain controversial. Moreover, the electrophysiological mechanism has not yet been identified. The aim of this study was to investigate the potential anti-arrhythmic and electrophysiological effects of the ET(A) receptor antagonist LU 135252 (LU) during myocardial ischaemia and reperfusion in a canine model. A bolus of LU (1 mg/kg; n=10) or saline (control; n=10) was injected into the left anterior descending coronary artery before ligation of this vessel for 30 min, which was followed by a 90-min reperfusion period. LU bolus administration (0.5 mg/kg) was repeated every 30 min. There were no differences in mean arterial blood pressure or coronary blood flow between the two groups. The determined left ventricular ischaemic mass was 25.5+/-1.8% and 27.8+/-2.2% of the total left ventricular mass in the control and LU groups respectively. The total incidence of ventricular fibrillation during ischaemia and reperfusion was 40% in the control and 50% in the LU group (not significantly different). The incidence of non-sustained and sustained ventricular tachycardias during ischaemia, reperfusion and over the whole period (ischaemia plus reperfusion) in the control group was 50%, 50% and 70% respectively, and that in the LU group was 80%, 70% and 100% respectively (no significant differences between groups). The number of ventricular premature beats was not decreased by LU during either ischaemia or reperfusion [median (25th-75th percentile): ischaemia, 20 (13-37) and 56 (32-130) for LU and control groups respectively; reperfusion, 15 (2-21) and 39 (7-74) respectively; ischaemia+reperfusion, 16 (4-35) and 43 (10-82) respectively; no significant differences between groups]. During ischaemia, the monophasic action potential duration at 90% repolarization (MAPD(90)) decreased significantly, while during reperfusion a significant prolongation of MAPD(90) was observed in the left anterior descending region that was similar in the two groups. In conclusion, LU did not affect repolarization changes and did not have anti-arrhythmic effects during either ischaemia or reperfusion in this model.

Action Potentials↗

Effects of implantable cardioverter defibrillator implantation and shock application on serum endothelin-1 and big-endothelin levels.

The incidence of ventricular tachyarrhythmias in the early post-operative period following implantable cardioverter-defibrillator (ICD) implantation is relatively high compared with that in control periods. Since endothelin-1 (ET-1) has been proven to be an endogenous arrhythmogenic substance, we investigated the changes in serum ET-1 and big-ET levels in patients undergoing ICD implantation. Serum concentrations of ET-1 and big-ET were measured in 14 patients with various heart diseases before the operation, as well as 1 min and 1 h after the last shock therapy. Big-ET levels and the sum of ET-1 and big-ET levels were unchanged immediately after the operation, but had increased significantly by 1 h after implantation (before, 1.57+/-0.61 pmol/l; 1 min, 1.86+/-0.87 pmol/l; 1 h, 4.29+/-1.65 pmol/l for big-ET; before, 3.44+/-1.07 pmol/l; 1 min, 3.79+/-1.29 pmol/l; 1 h, 6.36+/-2.03 pmol/l for big-ET+ET-1). There was a significant correlation between left ventricular ejection fraction and big-ET level measured 1 h after the last shock delivery (r=-0.542, P<0.05). We conclude that the increased big-ET level observed 1 h after the last induction and shock therapy of ventricular fibrillation might have a pathophysiological role in the increased incidence of post-operative spontaneous ventricular arrhythmias.

Aged↗

Permanent left atrial and left ventricular single-lead DDD pacing with a coronary sinus electrode.

This report describes a patient with drug refractory severe chronic congestive heart failure, first-degree AV block, and wide QRS complexes of 175-ms duration with left bundle branch block who was successfully treated by a left-sided dual chamber pacemaker system using a single-lead coronary sinus electrode. Left atrial and ventricular signal amplitudes, left atrial and ventricular pacing thresholds were 2.5 mV, 13 mV, 1.8 V and 0.7 V (0.5 ms), respectively. Using DDD pacing with an optimal 120-ms AV delay the QRS duration decreased to 150 ms and the mitral filling pattern improved. Three months after implantation the patient's functional status improved from NYHA Class III-IV to Class II.

Aged↗